S-phase fraction and nuclear size in long term prognosis of patients with breast cancer

Abstract

Background: S-phase fraction (SPF) predicts the prognosis of patients with breast cancer independently of tumor size, axillary metastasis, estrogen receptor (ER) and progesterone receptor (PgR), and patient age. Whether SPF is best measured by DNA labeling index (SPF-LI) or by flow cytometry (SPF-Flow) and what is the relative efficacy of SPF versus histopathologic characteristics for prognosis have remained unanswered questions.

Methods: The authors studied 845 women with Stages I-II disease classification for years 1975-1990 with end results data, who were treated surgically with axillary lymph node dissection by an in vitro DNA labeling index protocol with tritiated thymidine or 5-bromo-2'-deoxyuridine and whose SPF was measured microscopically. Nuclear size was estimated with a calibrated optical grid as less than 11 microns, 11-14 microns, or greater than 14 microns. DNA flow cytometry was performed on fresh or paraffin embedded tissue; ER and PgR were performed by cytosol assay. Kaplan-Meier survival plots and multivariate analysis were used for comparisons.

Results: Tumor size, axillary lymph nodal status, SPF-LI, nuclear size, and ER all related strongly to breast cancer specific survival and relapse free survival. PgR was less effective. Lymph node status and tumor size predicted long term survival; differences for other variables largely disappeared by 10 years. By multivariate analysis, axillary lymph node status, tumor size, and ER were independently prognostic for disease specific, relapse free survival. A strong trend was found for nuclear size. PgR, DNA ploidy, and SPF did not contribute to prognosis independently. Nuclear size was the strongest independent predictor in patients with negative axillary lymph nodes.

Conclusions: The number of positive axillary lymph nodes, tumor size, ER, and nuclear size were the strongest predictors of prognosis for patients with breast cancer. Only tumor size and lymph node status predicted the long term risk of metastasis.